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Review
. 2021 May 13;15(5):e0009340.
doi: 10.1371/journal.pntd.0009340. eCollection 2021 May.

Context-dependent roles of B cells during intestinal helminth infection

Aidil Zaini  1   2 , Kim L Good-Jacobson  1   2 , Colby Zaph  1   2
Affiliations
Review

Context-dependent roles of B cells during intestinal helminth infection

Aidil Zaini et al. PLoS Negl Trop Dis. .

Abstract

The current approaches to reduce the burden of chronic helminth infections in endemic areas are adequate sanitation and periodic administration of deworming drugs. Yet, resistance against some deworming drugs and reinfection can still rapidly occur even after treatment. A vaccine against helminths would be an effective solution at preventing reinfection. However, vaccines against helminth parasites have yet to be successfully developed. While T helper cells and innate lymphoid cells have been established as important components of the protective type 2 response, the roles of B cells and antibodies remain the most controversial. Here, we review the roles of B cells during intestinal helminth infection. We discuss the potential factors that contribute to the context-specific roles for B cells in protection against diverse intestinal helminth parasite species, using evidence from well-defined murine model systems. Understanding the precise roles of B cells during resistance and susceptibility to helminth infection may offer a new perspective of type 2 protective immunity.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. A paradigm of Th1/Th2 response during helminth infection.
During a Th2 cell-biased response, epithelial cell-derived cytokines such as TSLP and IL-33, in addition to tuft cell-derived IL-25, collectively result in the activation of type 2 response through Th2 cells and ILC2s. Once activated, these cells produce the type 2 cytokines IL-4, IL-5, and IL13 that in turn activate effector mechanisms for worm expulsion such as goblet cell hyperplasia, increased mucus production (Muc), muscle contractility, and production of RELM-β. In contrast, a Th1-biased response results in susceptibility. Activated IL-12-, IL-18-, and IL-27-induced Th1 cells (under some circumstances) robustly produce IFN-γ, which synergistically represses the type 2 response. IFN-γ, interferon gamma; ILC2, innate lymphoid cell 2; Muc, mucin; RELM-β, resistin-like molecules β; TSLP, thymic stromal lymphopoietin.
Fig 2
Fig 2. The protective roles of a GC-Tfh response during helminth infection.
During early stages of helminth infection, DCs in the lamina propria process the parasite-derived antigen, which then migrate to the MLNs. In MLNs, the DCs alongside B cells interact with naive CD4 T cells that result in Th2 and Tfh cell differentiation. In the presence of specific signals, Th2 cells are then localised to the effector sites and are predominantly responsible for the effector type 2-mediated worm expulsion response. On the other hand, Tfh cells interact with activated B cells for the formation of GC reactions in the MLNs. In the DZ, the B cells undergo further proliferation and SHM, resulting in higher affinity of B cell receptors. The B cells then migrate to the LZ and are selected by Tfh cells via specific interactions and Tfh-derived cytokines such as IL-4 and IL-21, to return to the DZ. Such a process occurs in an iterative fashion in order to produce an effective antibody repertoire such as IgG1 and IgE. The GC-Tfh cells can also differentiate into effector Th2 cells and vice versa. The GC-derived B cells can develop into long-lived memory B cells (Image created with Biorender.com). DC, dendritic cell; DZ, dark zone; GC, germinal center; ILC2, innate lymphoid cell 2; LZ, light zone; MLN, mesenteric lymph node; SHM, somatic hypermutation.
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Grants and funding

This work was supported by grants from the National Health and Medical Research Council of Australia (APP1104433 and APP1104466 to C.Z.), a Viertel-Belberry Senior Medical Research Fellowship (to K.L.G.-J.) and a Monash University Biomedicine Discovery Scholarship (to A.Z.). Salaries of A.Z. (Monash University) and K.L.G.-J. (Viertel-Belberry) were partially covered by funders. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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